Is APOB p.Pro955= (c.2865T>C) pathogenic?

APOB p.Pro955= (c.2865T>C) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Pro955= (c.2865T>C)?

APOB p.Pro955= (c.2865T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is APOB p.Pro955= (c.2865T>C) in the general population?

APOB p.Pro955= (c.2865T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

APOB p.Pro955=

c.2865T>C · rs2465398712 · VCV1796996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -0.98, phastCons 0.9
Overall
CADD	7.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,024 alleles

Overall 6.2e-05% 1/1,614,146 alleles · very rare exomes 1/1,461,886 · genomes 0/152,260 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOB
Protein: p.Pro955=
Coding: c.2865T>C
MANE Select: NM_000384
dbSNP: rs2465398712
Type: single nucleotide variant
Location: chr2:21019857 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 955: the 'heparin-binding' region; a UniProt-annotated variant site (in)

Full APOB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOB p.Pro955Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB p.Pro955Ala Uncertain significance ★ ⚠ same residue
APOB p.Pro955His Uncertain significance ★ ⚠ same residue
APOB p.Pro955Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB p.Arg490Trp Pathogenic/Likely pathogenic ★★ same condition
APOB c.1124+3A>G Uncertain significance ★★ same condition
APOB c.11788+4A>G Uncertain significance ★★ same condition
APOB c.12087+2T>C Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/apob-p-pro955 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown